This application seeks support for continued development of EMAN, an extensive image processing suite for electron microscopists. Structural biology is the study of the 3-D structure of individual molecules and biological nanoassemblies for the purpose of understanding their function and relating that function to cellular processes. Such studies are used both to provide a physical context to biochemistry as well as to study specific interactions, such as drugs interacting with target molecules, how viruses interact with cells or how biomolecules physically function. EMAN's primary use is for a technique known as single particle analysis, which merges thousands to hundreds of thousands of 2-D images of individual molecules/ assemblies to produce a high resolution 3-D reconstruction. EMAN has an installed user-base of over 1500 users worldwide, and includes a complete OpenGL based 3-D Graphical User Interface (GUI) built on an extensive library of hundreds of image processing algorithms. This application seeks continued support for the development of EMAN and for expanding its capabilities to make it useful to a broader range of researchers. We will support a number of new TEM methodologies, such as helical processing, random conical tilt and single particle tomography. In addition, we will connect EMAN's advanced GUI to several other specialized TEM image processing software tools, permitting users to seamlessly move data back and forth between the various packages, and use EMAN's advanced GUI to analyze and merge results. At present the process of using multiple software packages is exceptionally difficult and time consuming due to differing standards between the packages. We will establish the necessary data and convention translations to make such processing straightforward. EMAN is also beginning to be used as a component in software projects in other disciplines. This application will permit us to give assistance to these developers working to expand EMAN's usefulness to new biological communities. Finally, we will provide continuing support to our existing users, by enhancing documentation and extending EMAN's cross-platform support. Combined, these activities will serve to greatly enhance the productivity of this community and provide useful tools to new groups of NIH funded users. These methods are used in diverse areas of biology, and have expanded our understanding of diseases and conditions as diverse as neurodegeneration, heart disease and cancer.